PUBLICATION

The Calmodulin-Stimulated Adenylate Cyclase ADCY8 Sets the Sensitivity of Zebrafish Retinal Axons to Midline Repellents and Is Required for Normal Midline Crossing

Authors
Xu, H., Leinwand, S.G., Dell, A.L., Fried-Cassorla, E., and Raper, J.A.
ID
ZDB-PUB-100601-16
Date
2010
Source
The Journal of neuroscience : the official journal of the Society for Neuroscience   30(21): 7423-7433 (Journal)
Registered Authors
Raper, Jonathan
Keywords
none
MeSH Terms
  • Transfection
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/physiology*
  • Nerve Tissue Proteins/metabolism
  • Electroporation/methods
  • Chemokine CXCL12/pharmacology
  • Cell Movement/drug effects
  • Cell Movement/genetics
  • Cell Movement/physiology*
  • Retinal Ganglion Cells/cytology*
  • Retinal Ganglion Cells/drug effects
  • Retinal Ganglion Cells/metabolism
  • Chick Embryo
  • Cells, Cultured
  • Male
  • Cell Transplantation
  • Green Fluorescent Proteins/genetics
  • Oligoribonucleotides, Antisense/pharmacology
  • Animals
  • Female
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Mutation/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Animals, Genetically Modified
  • Colforsin/pharmacology
  • Zebrafish
  • Functional Laterality
  • Embryo, Nonmammalian
  • GAP-43 Protein/genetics
  • Adenylyl Cyclases/genetics
  • Adenylyl Cyclases/physiology*
  • Cyclic AMP/metabolism
  • Axons/drug effects
  • Axons/physiology*
  • Retina/cytology*
(all 36)
PubMed
20505109 Full text @ J. Neurosci.
Abstract
The chemokine SDF1 activates a cAMP-mediated signaling pathway that antagonizes retinal responses to the midline repellent slit. We show that knocking down the calmodulin-activated adenylate cyclase ADCY8 makes retinal axons insensitive to SDF1. Experiments in vivo using male and female zebrafish (Danio rerio) confirm a mutual antagonism between slit signaling and ADCY8-mediated signaling. Unexpectedly, knockdown of ADCY8 or another calmodulin-activated cyclase, ADCY1, induces ipsilateral misprojections of retinal axons that would normally cross the ventral midline. We demonstrate a cell-autonomous requirement for ADCY8 in retinal neurons for normal midline crossing. These findings are the first to show that ADCY8 is required for axonal pathfinding before axons reach their targets. They support a model in which ADCY8 is an essential component of a signaling pathway that opposes repellent signaling. Finally, they demonstrate that ADCY8 helps regulate retinal sensitivity to midline guidance cues.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s356tTgTransgenic Insertion
    te284
      Point Mutation
      ti272z
        Point Mutation
        zc7TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          Sequence Targeting Reagents
          Fish
          Antibodies
          Orthology
          Engineered Foreign Genes
          Marker Marker Type Name
          GFPEFGGFP
          1 - 1 of 1
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          Mapping